Julia, Sylvestre

The fact that the Julia-Lythgoe olefination requires more than one step to prepare alkenes has generally been accepted as an inconvenient and inevitable part of the procedure developed by Marc Julia and Basil Lythgoe. This flaw kept nagging at Marc Julia s brother Sylvestre, who would not rest until he had found the one-step (Sylvestre) Julia olefination. The (Sylvestre) Julia-Kocienski olefination has become the state-of-the-art-variant of this olefination (Figure 11.23). It may be applied to any kind of aldehyde. 

Marc) Julia-Lythgoe- and (Sylvestre) Julia-Kocienski Olefination... 

Julia-Lythgoe olefmation is probably the most important method for synthesizing acceptor-free, -configured alkenes, starting from an aldehyde and a primary alkylphenyl sulfone. In this two-step procedure, first the sulfone reacts with the aldehyde to form an acetyl-protected alcoholate and second this species undergoes Elcb elimination to afford the desired alkene. (Sylvestre) Julia olefination is a one-step procedure. It also affords -configured olefins from an aldehyde and an alkylsulfone as substrates, but is limited to base-resistant aldehydes. The most advanced variant is (Sylvestre) Julia-Kocienski olefination, which is also a one-step procedure and is applicable to all kinds of aldehydes. The mechanism is shown below. 

Potassium hexamethylsilazide is used as non-nucleophilic base to deprotonate 24 next to the sulfone. In the (Sylvestre) Julia olefmation the resulting C-nucleophile adds to the aldehyde and, in theory, the following steps of the mode of action yield the desired double bond -selectively by reductive elimination. In this case the Z-configured product was obtained as the major isomer. 

Bromobutenolide 18 and stannane 23 were connected in a Stille coupling followed by (Sylvestre) Julia olefination with sulfone 24 to complete this remarkable total synthesis of peridinin (1). 

Recent developments emphasise the convenience of replacing the three step (Marc) Julia reaction by one-step procedures using reagents 147 in which Ar is a heterocycle. Thus (Sylvestre) Julia used a benzothiazole 157. The adduct 158 with an aldehyde decomposes by fragmentation of the spiro compound 159 without the need for any further reagents to give S02, the alkene 150 and the benzothiazole 169. The benzene rings are omitted from 158-160 for clarity.31... 

The one-step heterocyclic modification of the Julia olefination was discovered by Marc Julia s brother, Sylvestre Julia, who also worked at the Ecole Normale Superieure. The use of tetrazolyl-sulfones was a contribution of Philip Kociehski, and the reaction is sometimes known as the Julia-Kocieilski reaction. 

In 1991, Sylvestre Julia reported a direct synthesis of olefins from carbonyl compounds and lithiated heterocyclic sulfones [132-134]. After the initial coupling... 

Sylvestre Julia and co-workers also found that the two diastereoisomers of the -hydroxy-BT-sulfones underwent elimination at different rates. The syn-isomer afforded the (Z)-alkene much faster than the anti-diastereoisomer produced the corresponding ( )-alkene. As can be seen in species 220 and 221, and are in an anti relationship during the transfer of the BT moiety of 218b. Further rotation about the central C-C bond is required to position the -OBT and -SO2 groups... 

Although these explanations were based upon reasonable assumptions, some observations can still not be accounted for, and Julia admitted that other reaction pathways might be followed in specific cases, such as in the coupling of BT-sulfones with arylaldehydes. To rationalize these anomalous results, Sylvestre Julia invoked the participation of benzyl-type carbocations followed by El-type elimination. Finally, S. Julia et al. studied the elimination of jS-hydroxy pyridinic sulfones and observed results analogous to those reported for the BT-sulfone derivatives (Scheme 3.44). 

The one-port olefination of Sylvestre Julia is operationally simpler and more amenable to scale up than the classical y4-step variant originally reported by Marc Julia. This reaction consists of the replacement of the phenyl sulfone moiety traditionally in the classical reaction, with different heteroaryl sulfones, such as benzothiazol-2-yl (BT, 5) sulfone. This allows the direct olefination process and eliminates the sulfone reduction step. The stereochemistry of the reaction in the synthesis of 1,2-disubstituted alkenes is dependent on the base and solvent. 

Sylvestre Julia and co-workers discoveried in 1991 a direct synthesis of olefins by reaction of carbonyl compounds with lithio derivatives of 2-[alkyl- or (2 -alkenyl)- or benzyl-sulfonylj-benzothiazoles (BT, 5). Since the initial study of the reaction of metallated BT sulfone 5 with carbonyl compounds, the versatility of these derivatives has been fully demonstrated through their application in the total synthesis of a large number of nature products. Kocienski and co-workers found in 1998 that l-phenyl-17/-tetrazol-5-yl sulfone (PT, 6) is a better olefination partner comparing to BT sulfones. This allowed the one-port Julia-Lythgoe olefination to be employed more efficiently and broadly, especially in the synthesis of nature products. 

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